Blood creatinine content and rat kidney structure after intramuscular injection of pegylated antibiotic enrofloxacin

Abstract

Background. Polyethylene glycol (PEG) is able to affect the permeability of memb­ra­nes by increasing the entry of antibiotics into the cell of microorganism; therefore, PEGylation may improve the effectiveness of antibiotics due to chemical modification of their molecules. It is important to assess the safety and toxicity of new compounds for drug development activity. The aim of this research was to study the functional state and structure of the kidneys of laboratory rats after intramuscular administration of PEGylated antibiotic enrofloxacin, as well as commercial antibiotic enrofloxacin and polymer PEG-400, which were used for the synthesis of PEGylated antibiotic enrofloxacin. Materials and Methods. PEGylated antibiotic enrofloxacin was obtained via the reaction between enrofloxacin chloride and PEG-400 polymer (polyethylene glycol with a molecular weight of 400 Da). The research was conducted on four groups of rats: control and three experimental ones, 12 animals in each group. Physiological saline solution was intramuscularly injected to the control rats; commercial antibiotic enrofloxacin – to rats of the first experimental group; polymer PEG-400 – to rats of the second experimental group; PEGylated antibiotic enrofloxacin – to rats of the third experimental group. Results. The conducted studies did not show a significant difference between the serum creatinine in control rats and experimental ones on the 7th, 14th and 21st days after the last administration of the drugs. Creatinine levels in the blood of all groups of animals were within physiological ranges. Histological studies of the kidney structure in control rats indicated no changes during the experiment. Histological changes in the structure of the kidneys were observed within the first seven days after the end of the intramuscular administration of polymer PEG-400 and PEGylated antibiotic enrofloxacin. Injections of the commercial form of antibiotic enrofloxacin to experimental rats caused histological changes in the kidney structure for 21 days of the experiment. Conclusions. Quadruple intramuscular administration of PEGylated and commercial antibiotics enrofloxacin to rats showed that PEGylation reduces nephrotoxicity and shortens the duration of adverse effects in the kidneys.